Cross-Species Transmission of a Novel Adenovirus Associated with a Fulminant Pneumonia Outbreak in a New World Monkey Colony

Adenoviruses are DNA viruses that naturally infect many vertebrates, including humans and monkeys, and cause a wide range of clinical illnesses in humans. Infection from individual strains has conventionally been thought to be species-specific. Here we applied the Virochip, a pan-viral microarray, to identify a novel adenovirus (TMAdV, titi monkey adenovirus) as the cause of a deadly outbreak in a closed colony of New World monkeys (titi monkeys; Callicebus cupreus) at the California National Primate Research Center (CNPRC). Among 65 titi monkeys housed in a building, 23 (34%) developed upper respiratory symptoms that progressed to fulminant pneumonia and hepatitis, and 19 of 23 monkeys, or 83% of those infected, died or were humanely euthanized. Whole-genome sequencing of TMAdV revealed that this adenovirus is a new species and highly divergent, sharing <57% pairwise nucleotide identity with other adenoviruses. Cultivation of TMAdV was successful in a human A549 lung adenocarcinoma cell line, but not in primary or established monkey kidney cells. At the onset of the outbreak, the researcher in closest contact with the monkeys developed an acute respiratory illness, with symptoms persisting for 4 weeks, and had a convalescent serum sample seropositive for TMAdV. A clinically ill family member, despite having no contact with the CNPRC, also tested positive, and screening of a set of 81 random adult blood donors from the Western United States detected TMAdV-specific neutralizing antibodies in 2 individuals (2/81, or 2.5%). These findings raise the possibility of zoonotic infection by TMAdV and human-to-human transmission of the virus in the population. Given the unusually high case fatality rate from the outbreak (83%), it is unlikely that titi monkeys are the native host species for TMAdV, and the natural reservoir of the virus is still unknown. The discovery of TMAdV, a novel adenovirus with the capacity to infect both monkeys and humans, suggests that adenoviruses should be monitored closely as potential causes of cross-species outbreaks

Native American Ancestry and Air Pollution Interact to Impact Bronchodilator Response in Puerto Rican Children with Asthma.

ObjectiveAsthma is the most common chronic disease in children. Short-acting bronchodilator medications are the most commonly prescribed asthma treatment worldwide, regardless of disease severity. Puerto Rican children display the highest asthma morbidity and mortality of any US population. Alarmingly, Puerto Rican children with asthma display poor bronchodilator drug response (BDR). Reduced BDR may explain, in part, the increased asthma morbidity and mortality observed in Puerto Rican children with asthma. Gene-environment interactions may explain a portion of the heritability of BDR. We aimed to identify gene-environment interactions associated with BDR in Puerto Rican children with asthma.SettingGenetic, environmental, and psycho-social data from the Genes-environments and Admixture in Latino Americans (GALA II) case-control study.ParticipantsOur discovery dataset consisted of 658 Puerto Rican children with asthma; our replication dataset consisted of 514 Mexican American children with asthma.Main outcome measuresWe assessed the association of pairwise interaction models with BDR using ViSEN (Visualization of Statistical Epistasis Networks).ResultsWe identified a non-linear interaction between Native American genetic ancestry and air pollution significantly associated with BDR in Puerto Rican children with asthma. This interaction was robust to adjustment for age and sex but was not significantly associated with BDR in our replication population.ConclusionsDecreased Native American ancestry coupled with increased air pollution exposure was associated with increased BDR in Puerto Rican children with asthma. Our study acknowledges BDR's phenotypic complexity, and emphasizes the importance of integrating social, environmental, and biological data to further our understanding of complex disease

Integrative genomic analysis in African American children with asthma finds three novel loci associated with lung function.

Bronchodilator (BD) drugs are commonly prescribed for treatment and management of obstructive lung function present with diseases such as asthma. Administration of BD medication can partially or fully restore lung function as measured by pulmonary function tests. The genetics of baseline lung function measures taken before BD medication have been extensively studied, and the genetics of the BD response itself have received some attention. However, few studies have focused on the genetics of post-BD lung function. To address this gap, we analyzed lung function phenotypes in 1103 subjects from the Study of African Americans, Asthma, Genes, and Environment, a pediatric asthma case-control cohort, using an integrative genomic analysis approach that combined genotype, locus-specific genetic ancestry, and functional annotation information. We integrated genome-wide association study (GWAS) results with an admixture mapping scan of three pulmonary function tests (forced expiratory volume in 1 s [FEV1 ], forced vital capacity [FVC], and FEV1 /FVC) taken before and after albuterol BD administration on the same subjects, yielding six traits. We identified 18 GWAS loci, and five additional loci from admixture mapping, spanning several known and novel lung function candidate genes. Most loci identified via admixture mapping exhibited wide variation in minor allele frequency across genotyped global populations. Functional fine-mapping revealed an enrichment of epigenetic annotations from peripheral blood mononuclear cells, fetal lung tissue, and lung fibroblasts. Our results point to three novel potential genetic drivers of pre- and post-BD lung function: ADAMTS1, RAD54B, and EGLN3

Whole-Genome Sequencing Identifies Novel Functional Loci Associated with Lung Function in Puerto Rican Youth.

Rationale: Puerto Ricans have the highest childhood asthma prevalence in the United States (23.6%); however, the etiology is uncertain.Objectives: In this study, we sought to uncover the genetic architecture of lung function in Puerto Rican youth with and without asthma who were recruited from the island (n = 836).Methods: We used admixture-mapping and whole-genome sequencing data to discover genomic regions associated with lung function. Functional roles of the prioritized candidate SNPs were examined with chromatin immunoprecipitation sequencing, RNA sequencing, and expression quantitative trait loci data.Measurements and Main Results: We discovered a genomic region at 1q32 that was significantly associated with a 0.12-L decrease in the lung volume of exhaled air (95% confidence interval, -0.17 to -0.07; P = 6.62 × 10-8) with each allele of African ancestry. Within this region, two SNPs were expression quantitative trait loci of TMEM9 in nasal airway epithelial cells and MROH3P in esophagus mucosa. The minor alleles of these SNPs were associated with significantly decreased lung function and decreased TMEM9 gene expression. Another admixture-mapping peak was observed on chromosome 5q35.1, indicating that each Native American ancestry allele was associated with a 0.15-L increase in lung function (95% confidence interval, 0.08-0.21; P = 5.03 × 10-6). The region-based association tests identified four suggestive windows that harbored candidate rare variants associated with lung function.Conclusions: We identified common and rare genetic variants that may play a critical role in lung function among Puerto Rican youth. We independently validated an inflammatory pathway that could potentially be used to develop more targeted treatments and interventions for patients with asthma

Внешнеэкономическое сотрудничество России и Казахстана: от истории к современности

Abstract: Предмет/тема. Россия и Казахстан являются странами, имеющими тесные партнерские политические и экономические отношения в разных форматах: ЕАЭС и Таможенного союза, а также ОДКБ и СНГ. У России и Казахстана имеется общий рынок, отсутствует таможенная граница, могут свободно перемещаться товары, услуги, рабочая сила, но, несмотря на эту внешнюю открытость, не решен ряд проблем, связанных с современной экономической и политической ситуацией. В статье проанализированы тенденции внешней торговли между двумя странами, освещены основные проблемы внешнеэкономического сотрудничества России и Казахстана. Актуальность темы исследования обусловлена тем, что в 2017-2018 гг. наблюдается несоответствие между экономическими и политическими линиями развития Российской Федерации и Республики Казахстан, что негативно влияет на внешне-экономические, политические и культурные связи России. Цели/задачи. Целями данной статьи является исследование исторических аспектов и современных реалий двусторонних отношений между Республикой Казахстан и Российской Федерацией; выявление факторов, оказывающих влияние на усиление экономического и политического неравенства между Россией и Республикой Казахстан, которое отрицательно сказывается на исторически дли-тельные отношения между странами, что, в свою очередь, отрицательно влияет как на внешнюю торговлю, так и на социокультурный обмен. Методология. Методической основой являются литературные источники по теме исследования, а также открытые аналитические материалы. Методами исследования являются общенаучные методы анализа и синтеза. Результаты. В настоящей статье авторы приходят к выводу, что решение ряда проблем, возникших в процессе внешнеэкономического сотрудничества России и Казахстана, кроется в формировании надгосударственного института агентов экономической дипломатии. Такой институт обеспечит согласованность интересов политических дипломатов и деловых кругов, а также может явиться основой для выработки рекомендаций в области координации важнейших направлений стратегического развития Российской Федерации и Республики Казахстан. Выводы/значимость. Проведенное исследование исторических и современных аспектов двусторонних отношений между Российской Федерацией и Республикой Казахстан позволило сделать следующие важные выводы. Во-первых, Россия и Казахстан, несмотря на негативные исторические аспекты совместного развития, смогли сформировать единое и относительно эффективное экономическое пространство, использующее преимущества сотрудничества, созданного в советское время. Во-вторых, Казахстан нуждается в большем развитии двусторонних экономических отношений (в том числе в рамках единого таможенного пространства) в большей степени, чем Россия, поскольку это зависит от внешней торговли с Российской Федерацией. В-третьих, Россия, находящаяся под внешне-политическим и внешнеэкономическим давлением со стороны европейских стран и США, нуждается в поддержке со стороны Республики Казахстан, а также стран, вступающих в Таможенный союз и Евразийский экономический союз. Применение. Полученные выводы и результаты исследования могут быть использованы при решении проблем, связанных с современной экономической и политической ситуацией в мире и в странах ЕАЭС в целом. Статья подготовлена в рамках государственного задания ИПР РАН, тема НИР «Социально-экономическое и научно-технологическое развитие на разных уровнях управления в отраслях, комплексах и сферах деятельности национального хозяйства России»

Genetic Determinants of Telomere Length in African American Youth.

Telomere length (TL) is associated with numerous disease states and is affected by genetic and environmental factors. However, TL has been mostly studied in adult populations of European or Asian ancestry. These studies have identified 34 TL-associated genetic variants recently used as genetic proxies for TL. The generalizability of these associations to pediatric populations and racially diverse populations, specifically of African ancestry, remains unclear. Furthermore, six novel variants associated with TL in a population of European children have been identified but not validated. We measured TL from whole blood samples of 492 healthy African American youth (children and adolescents between 8 and 20 years old) and performed the first genome-wide association study of TL in this population. We were unable to replicate neither the 34 reported genetic associations found in adults nor the six genetic associations found in European children. However, we discovered a novel genome-wide significant association between TL and rs1483898 on chromosome 14. Our results underscore the importance of examining genetic associations with TL in diverse pediatric populations such as African Americans

Ambient air pollution, asthma drug response, and telomere length in African American youth.

BackgroundTelomere length (TL) can serve as a potential biomarker for conditions associated with chronic oxidative stress and inflammation, such as asthma. Air pollution can induce oxidative stress. Understanding the relationship between TL, asthma, and air pollution is important for identifying risk factors contributing to unhealthy aging in children.ObjectivesWe sought to investigate associations between exposures to ambient air pollutants and TL in African American children and adolescents and to examine whether African ancestry, asthma status, and steroid medication use alter the association.MethodsLinear regression was used to examine associations between absolute telomere length (aTL) and estimated annual average residential ozone (O3) and fine particulate matter with a diameter of 2.5&nbsp;μm or less (PM2.5) exposures in a cross-sectional analysis of 1072 children in an existing asthma case-control study. African ancestry, asthma status, and use of steroid medications were examined as effect modifiers.ResultsParticipants' aTLs were measured by using quantitative PCR. A&nbsp;1-ppb and 1&nbsp;μg/m3 increase in annual average exposure to O3 and PM2.5 were associated with a decrease in aTL of 37.1 kilo-base pair (kb; 95% CI, -66.7 to -7.4 kb) and 57.1 kb (95% CI, -118.1 to 3.9 kb), respectively. African ancestry and asthma were not effect modifiers; however, exposure to steroid medications modified the relationships between TL and pollutants. Past-year exposure to O3 and PM2.5 was associated with shorter TLs in patients without steroid use.ConclusionExposure to air pollution was associated with shorter TLs in nonasthmatic children and adolescents. This was not the case for asthmatic children as a group, but those receiving steroid medication had less shortening than those not using steroids. Reduced exposure to air pollution in childhood might help to preserve TL